NEODOSE

INDICATIONS

• Anticonvulsant: PHENobarbital is the first-line agent for neonatal seizures. The second-line agents, when seizures are not controlled with the maximal tolerated dose of PHENobarbital, are a benzodiazepine, phenytoin, or lidocaine. PHENobarbital reduced electrographic seizure burden within 1 hour of administration and for a duration of up to 4 hours (n=19) .
• Cholestasis: During first course therapy, ursodiol reduced direct bilirubin by 1.89 mg/dL compared with an increase of 0.76 mg/dL (p = 0.03) for PHENobarbital in a retrospective study of 68 preterm and term newborns with direct bilirubin greater than 3 mg/dL. The change for all treatment courses were -3.96 mg/dL for ursodiol and +0.28 mg/dL for PHENobarbital. Median dosages were ursodiol 27.43 mg/kg/day enterally and PHENobarbital 4.48 mg/kg/day IV .
• Neonatal abstinence syndrome (NAS): In nonopiate- or polydrug-exposed infants . In a prospective, randomized, open-label trial, infants 35 weeks gestational age or older treated with morphine for NAS experienced shorter morphine treatment days (4.6 less days (95% CI, 0.3 to 8.9 days)) and no difference in morphine total dose with adjunctive PHENobarbital compared with cloNIDine. However, the total duration of PHENobarbital therapy continued for an average of 3.8 months (range 1 to 8 months). Sublingual buprenorphine was associated with the largest reduction in length of treatment and length of stay for NAS in a network meta-analysis of 18 randomized controlled trials (n=1072) of buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Morphine was the least effective opioid. The findings should be interpreted with caution due to significant study limitations. May enhance bile excretion in patients with cholestasis before 99Tc-IDA scanning.

CONTRAINDICATIONS

Contraindicated in patients with manifest or latent porphyria, marked liver function impairment, or respiratory disease with dyspnea or obstruction .

ADVERSE EFFECTS

Sedation at serum concentrations above 40 mcg/mL. Respiratory depression at concentrations above 60 mcg/mL. Irritating to veins – pH is approximately 10 and osmolality is approximately 15,000 mOsm/kg H2O.

ADMINISTRATION

• Intravenous: Administer IV over 15 to 30 minutes at a concentration of 10 mg/mL or 65 mg/mL . PHENobarbital sodium can be diluted to 10 mg/mL in normal saline prior to administration .
• Oral: The intravenous formulation of PHENobarbital, diluted to 10 mg/mL, has been used orally. An extemporaneous PHENobarbital suspension can also be used to avoid alcohol content in the PHENobarbital oral and IV solution (See Special Considerations/Preparation)

MONITORING

PHENobarbital monotherapy will control seizures in 43% to 85% of affected neonates – adding a second drug (phenytoin or lorazepam) is often needed. Therapeutic serum concentration is 15 to 40 mcg/mL. Drug accumulation may occur using recommended maintenance dose during the first two weeks of life. Altered (usually increased) serum concentrations may occur in patients also receiving phenytoin or valproate. Observe IV site for signs of extravasation and phlebitis. In infants with neonatal abstinence syndrome, serum concentrations of 20 to 30 mcg/mL are associated with adequate symptom control.